Process of manufacturing a heart valve made of a polymeric material and the heart valve thereby obtained

ABSTRACT

A process for the manufacture of a heart valve of polymer material which provides for the deposition of a polymer solution comprising a copolymer which is preferably a copolymer of poly(carbonato-urethane) fluoridate (F-PCU) and intracatenary polydimethylsiloxane (PDMS), a PDMS with a functional group outside the chain and a solvent onto a mould using a spray technique associated with phase inversion.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a U.S. National Phase Application under 35U.S.C. § 371 of International Application No. PCT/IB/2015/054568, filedJun. 17, 2015, entitled A PROCESS OF MANUFACTURING A HEART VALVE MADE OFA POLYMERIC MATERIAL AND THE HEART VALVE THEREBY OBTAINED, which claimspriority to Italian Patent Application No. TO2014A000479, filed Jun. 17,2014.

FIELD

This invention in general relates to the sector of cardiovasculardevices; in particular the invention relates to a technique for themanufacture of heart valves through the use of polymer materials.

BACKGROUND

Valve replacements are among the most widely used cardiovascular devicesand the demand for them is increasing. At the present time the clinicaldevices available are limited to mechanical and biological valves.Long-term clinical applications of such valves are however highlyproblematic, given some persistent critical problems such asthrombogenicity and service life.

In fact mechanical valves have a service life and do not need repeatsurgery, in that they are not subject to structural failures, butbecause they give rise to thromboembolic complications patients have totake anticoagulant treatments for their entire lives. Biological valveprostheses made of porcine, bovine or equine pericardium modelled andsutured onto support structures (stents) reproduce the functionalbiomechanical characteristics of native valves, give rise to fewerthromboembolic complications but in many cases have to be replaced 10-15years after implant because of the occurrence of calcification problemsand damage brought about by the decellularisation treatments undergonein order to reduce problems associated with immunological response.

The use of xenografts (whole valves taken from animals) and homografts(whole valves taken from cadavers) has hitherto been limited byrejection problems and very low availability.

Polymeric heart valves (hereinafter PHV) have been investigated for along time, but their success has been impeded by very short service lifedue to problems with calcification, thromboembolic complications andinsufficient mechanical properties of the leaflets which are the causeof malfunctioning during the stages of opening/closing. They havehowever found use which is limited to devices for ventricular assistancefor temporary use. Use in these systems is in fact less critical becausethey are intended for temporary paracorporeal use (months, or at mostvery few years) and the patients nevertheless always receiveanticoagulant therapy.

Ideally a PHV should combine the service life of mechanical valves andthe haemocompatibility of biological valves, overcoming thedisadvantages, mainly the thrombogenicity of mechanical valves and thepoor service life of biological valves. Also new emerging therapeuticalternatives such as valve replacement by a minimally invasivepercutaneous approach, which require devices capable of being collapsedand introduced within small diameter catheters, have attracted greaterattention to the PHV option. Another new concept in valve replacementtherapy, the tissue engineering of PHV, which uses biodegradablesynthetic polymers as a scaffold, has recently increased interest inpolymer materials.

Choice of material is important for the development of PHV because thematerial helps to provide the valve with durability andbiocompatibility, so as to overcome the clinical problems associatedwith both mechanical and biological valves, such as thromboembolicevents, undesired events due to anticoagulants and premature failure,providing improved haemodynamic functionality and service life.

Thus because a PHV is becoming a valid alternative option to valvereplacement therapy the polymer selected must not only have acceptablecharacteristics with regard to biostability, haemocompatibility,anti-thrombogenicity, resistance to degradation and calcification, itmust also have good affinity for endothelial cells.

Various synthetic polymers have been used as materials for valveleaflets, including inert synthetics such as silicone and polyolefinrubber, but these have proved to have an inadequate service life andhave therefore been subsequently abandoned. Polytetrafluoroethylene(PTFE) has not had success as a material for PHV for similar reasons, inthat it has given rise to a high incidence of thrombosis andcalcification.

Polyurethanes (PU) are among the most popular and successful materialsfor biomedical applications. This class of polymer materials in fact hasa number of favourable properties deriving from a two-stagemicrostructure consisting of rigid crystalline segments and softelastomer segments, the ratio between which gives rise to importantproperties of the material such as rigidity. The rigid segments areformed by the reaction of a diisocyanate with a short chain diol ordiamine (“chain extenders”) typically 1,4-butanediol or ethylenediamine. The soft segments are formed by the reaction of diisocyanatewith high molecular weight polyols typically within the range of1000-2000 Daltons, such as polyethers, polyesters or polycarbonates.Their versatile characteristics, such as for example haemocompatibilityand improved haemodynamic and mechanical properties, make PU usefulmaterials for the development of cardiovascular devices.

However the main disadvantage associated with long-term applications istheir low biostability, which is mainly caused by their susceptibilityto degradation. The degradation of PUs is brought about by oxidation,acid hydrolysis or enzyme sequences and results in the loss ofmechanical properties and eventually the creation of lacerations orcracks in the valve leaflets. The second and more serious disadvantageof PU is their tendency to calcification, which remains an appreciableobstacle to their use in long-term implants.

In order to deal with these problems efforts have been made to improvethe properties of polyurethanes by modifying the soft segments, whichare considered to be the most vulnerable components. Up to now threemain types of PU with different soft segments, that is polyesterurethanes (PEsU), polyether urethanes (PEtU) and polycarbonate urethanes(PCU) have been developed and consequently tested in biomedicalapplications.

The first generation of PU used in medical devices were the PEsU, butthese proved unsuitable for long-term implants because of rapidhydrolysis of the soft polyester segment. PEtU on the contrary haveexcellent stability to hydrolysis and have therefore replaced PEsU inimplantable medical devices for a couple of decades.

However, recently various studies have demonstrated that the softsegment of polyether is also susceptible to oxidative degradation andsuffers environmental stress cracking under the conditions of in vivoimplants.

Subsequently the third class of PUs, PCUs, have been tested and havedemonstrated that they have greater stability to oxidation. Incomparison with PEtUs the degree of biodegradation of PCUs has proved tobe significantly lower and restricted to a thin surface layer.Replacements of the chemical structure of PUs have also been made in anattempt to increase their biostability. The, binding ofbiodegradation-resistant molecules to the polymer has proved aneffective method for increasing the biostability of PUs. For exampleattempts have been made to incorporate polydimethylsiloxane (PDMS) (amolecule which imparts good thermal and oxidative stability) into the PUchain in the presence of polyhexamethylene oxide (PHMO), which is acompatibilising polyether facilitating incorporation of the non-polarPDMS macrodiol into the PU.

The idea underlying this proposed patent is the development of a newdesign of PHV with a geometry similar to that of a natural aortic valve(and therefore that of biological valve prostheses) which is not subjectto calcification, has a long service life and a morphology such as toreduce the thromboembolic complications due to its interaction withblood flow and with cardiac and vascular tissue to a minimum.

The valve, a single body incorporated with the supporting stent, is madeusing a semi-interpenetrating polymer network (semi-IPN) newlysynthesised on the basis of a co-polymer of poly(carbonate-urethane)(PCU) and polymethylsiloxane (PDMS), cross-linked with a functionalisedsilicone (functional-PDMS) and capable of combining the best mechanicalstrength, biocompatibility and superior biostability properties of PCUwith the excellent haemocompatibility and calcification-resistanceproperties of silicone (PDMS) as a material of manufacture.

The presence of silicone in the polyurethane chain, together with thatof the cross-linking silicone forming the semi-IPN makes it possible tovary the flexibility (flex-life) and biodegradation resistance of thenew valves.

As far as the design of PHV is concerned, it is well known that thestructural anatomy of the natural valve plays an essential part in itsoperating function, providing a suitable and stable structure withspecific anatomical and histological characteristics. In view of thecomplex anatomy of natural valves it is difficult to create structureswhich have the precise anatomical and functional characteristics of anative valve. However, unlike their biological counterparts, valves withsynthetic leaflets can be designed in virtually any form, and thisemphasises the possible importance of structural design strategies.

The process of valve manufacture is also an essential factor influencingthe performance of PHV, as its effect on the durability of valves andtheir haemodynamic functions has been demonstrated.

Different methods of producing PHV have been investigated, such as deepcoating, film-fabrication, cavity moulding and injection moulding.

Deep-coating implies the use of a specifically designed former whichundergoes repeated cycles of immersion in the polymer solution andsubsequent consolidation in air or in a dry air stove until the desiredthickness is achieved. The concentration of the polymer solution mayvary according to the polymer chosen and the stage of manufacture.Normally the deep-coating process comprises repeated immersion in a lowconcentration polymer solution.

The great disadvantage of this method is that it is difficult to controlthe thickness distribution in the leaflet precisely. Some have proposedthat leaflets should be made using a single immersion in concentratedpolymer solution. This would allow more accurate reproducibility andwould reduce dependence on the operator to a minimum, but because of theconcentrated polymer solution undesired densification of the material indifferent portions of the leaflets could occur.

In film-fabrication, polymer films are deposited up to a particularthickness and the leaflets are produced by cutting the film to thedesired shape. The leaflets are then anchored to the valve supportstructure, which is manufactured separately, through the use ofsolvents. Finally a thermal shaping process is used to obtain thedesired valve geometry. A potential disadvantage of this technique liesin the weaknesses which may be created at the point where the leafletsare anchored to the structure of the valve because of the use of polymersolvent.

Cavity moulding uses a cavity mould comprising a static portion (female)and a moving portion (male); the mould is used to manufacture the entirevalve structure through introducing hot polymer, after which the sealedmould is placed in a water bath and subjected to alternating freeze/thawcycles to form a thin polymer film.

The disadvantage of this method lies in the fact that the material hasto be subjected to different thermal cycles which could affect thefatigue resistance characteristics of the valve in a manner which isdifficult to foresee.

In injection moulding an injection moulding machine is used tomanufacture the valve leaflets in a partly open position on a former,after which repeated baths of hot and cold water are applied in order toproduce the final valve. Here again the repeated thermal cycles mayaffect the mechanical and biostability characteristics of the valve.

Understandably these limitations make it difficult to manufacture heartvalves having high durability and haemocompatibility standards.

SUMMARY OF THE INVENTION

One object of this invention is to overcome the limitations mentionedabove through a PHV which has been obtained with the help ofspray-machine technology capable of producing three-dimensionalstructures starting from polymer solutions.

The spray-machine comprises a precision lathe capable of housingrotating formers and two spray-guns which may be positioned on acarriage capable of lateral motion so as to spray the components listedin paragraphs 1) and 2) below at the same time but separately.

1) A copolymer solution as defined in paragraph e) of appended claim 1,in which the copolymer is present in a concentration of preferablybetween 1 and 3% (w/v) per volume of solution. In a preferred embodimentthe copolymer solution solvent is selected from the group comprisingtetrahydrofuran (THF), dioxan (DX), dimethylacetamide (DMAc) and theirmixtures. Particularly preferred solvents are 1:1 (v/v) mixtures of THFand DX and of THF and DMAc. In the case of PCU-PDMS copolymer theintrachain silicone is preferably present as 20% (w/w) of the totalweight of the copolymer. A variable quantity, preferably from 30 to 60%(w/w), of an extrachain functionalised silicone as defined in paragraphe) of appended claim 1 is added to the above solution. Theabovementioned quantity relates to the total weight of copolymer. Inanother preferred embodiment the PCU-PDMS copolymer (e.g. 20%intrachain) ends in fluorine atoms (fluoridate) and a variable quantity,preferably from 30 to 60% (w/w) of an extrachain functionalised siliconecan also be added to this formulation.

2) A non-solvent for the polymer solution, preferably selected fromwater and an alcohol and their mixtures; the alcohol is for exampleethyl alcohol, propyl alcohol, benzyl alcohol, etc.

In another preferred embodiment the non-solvent may contain apolysaccharide polymer in solution, for example a polysaccharide polymercomprising repeated units of maltotriose, known as pullulan, and/orgelatin. The substances dissolved in the non-solvent are incorporatedinto the synthetic matrix of the PHV during spray deposition and may besubsequently cross-linked to stabilise their structure within thesynthetic matrix. For example, in the case of the incorporation ofgelatin, once it has formed the PHV is exposed to glutaraldehyde vapoursto cross-link the gelatin without direct contact with the cross-linkingagent. The glutaraldehyde is then neutralised by repeated washing inglycine. In this way PHV containing gelatin and/or pullulan represent anoptimum substrate for tissue engineering.

Merely by way of information and without limitation, a more detaileddescription of the abovementioned PCU-PDMS copolymer and itscross-linking reaction is provided below.

PCU-PDMS is a polycarbonate-urethane-silicone thermoplastic blockcopolymer containing silicone as a soft segment. The copolymer issynthesised by means of a continuous process through which the silicone[polydimethylsiloxane (PDMS)] is incorporated in the soft segment of thepolymer together with an aliphatic polycarbonate with a terminalhydroxyl group. The rigid segment is formed of an aromatic diisocyanate[diphenylmethane-4,4′-diisocyanate (MDI)], together with a low molecularweight glycol as a chain extender. The copolymer chains, formed ofblocks based on 4,4′-bis-diphenol-2,2′-propane carbonate ester, mayterminate in either silicone or fluorine.

A variable quantity of from 30 to 60% of a silicone with a di-acetoxysilyl termination (functional tetra-acetoxy) which is capable ofreacting with other molecules of the same species in the presence ofwater forming PDMS cross-linking which is semi-interpenetrating with thePCU molecule is added to the above material with either a silicone orfluorine (fluoridate) terminal group.

Cross-linking of the PDMS with extrachain functional groups initiated bythe non-solvent (for example water) during the spray deposition processis completed by standing a valve device in water heated to approximately60° C. while the solvent is removed, or by placing it in a heated stoveand subsequently standing it in water heated to approximately 60° C.

The spray-guns focus their jets at a specific point on the former. Aspray machine having similar characteristics is described in EP 1 431019.

Intersection of the flows induces rapid precipitation of the polymeronto the former (phase inversion), faithfully reproducing its geometryand making it possible to generate a three-dimensional “non-woven”filamentous structure which can have different porosities, propertiesand morphological characteristics depending upon the adjustment of themanufacturing variables.

PHV obtained using this technology can be effectively stored even indehydrated form to be rehydrated at the time of use, and in hydratedform, keeping them immersed in aqueous solution.

The valve obtained by the process according to this invention ischaracterised by the fact that it comprises a single piece and has nodiscontinuities, and therefore results in very good haemocompatibility,as well as not requiring chronic anticoagulant treatment, and areliability and service life such as to allow it to be implanted into ahuman being or animal as a permanent valve prosthesis.

The above and other objects and advantages are accomplished according toone aspect of the invention by a system having the characteristicsdefined in claim 1. Preferred embodiments of the invention are definedin the dependent claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The functional and structural characteristics of some preferredembodiments of a technique for the manufacture of polymeric heart valvesaccording to the invention will now be described. Reference will be madeto the appended drawings, in which:

FIGS. 1A and 1B are diagrammatical perspective views of a polymericheart valve obtained by an embodiment of the process according to theinvention, in the open and closed configurations;

FIGS. 2A and 2B are diagrammatical perspective views of a mould andsupport for the manufacture of the valve illustrated in FIGS. 1A and 1B;

FIG. 3 shows a partial functional diagram of equipment for manufacturingthe polymeric heart valve in the preceding figures according to anembodiment of the process according to the invention;

FIGS. 4A, 4B and 4C are diagrammatical perspective views of details ofthe machine in FIG. 3 during particular stages in the process accordingto the invention;

Figures from 5A to 5F are diagrammatical perspective views of somestages in the process according to one embodiment of the invention.

DETAILED DESCRIPTION

Before explaining the plurality of embodiments of the invention indetail, it must be pointed out that in its application the invention isnot limited to the construction details and configurations of componentsdescribed in the description below or illustrated in the drawings. Theinvention is capable of adopting other embodiments and being implementedor carried out in practice in different ways. It should also beunderstood that the phraseology and terminology are of a descriptivenature and should not be understood as being limiting. The use of“includes” and “comprises” and their variations are to be understood asincluding the items listed below and their equivalents, as well asadditional elements and their equivalents.

Initially with reference to FIG. 1, a polymeric heart valve 9 comprisesan annular support 10 and a plurality of flexible leaflets or leaflets12, shaped so as to form a Y-shaped through passage 14. This passage 14dilates and closes as the upper edges 12 a of leaflets 12 move apart ortogether in such a way as to allow rather than inhibit the blood flowpassing through valve 9.

Annular support 10 (which can be seen in FIG. 2B), generally comprises alower ring 10 a on which there is mounted a wavy crown formed of threerounded projections 10 b, joined together at the bottom by archedsections 10 c. From tests made to prevent tearing of valve leaflets 12,rounded projections 10 b must have a height of between 13 and 3 mmmeasured from the apex of projection 10 b to the base of the crown (orlower ring 10 a). If projections 10 b are of shorter height the crown ismore level, and as a consequence there is a smaller concentration ofstresses loading the joining lines between the crown and leaflets.

The overall architecture of the valve, which is in itself known, willnot be further described.

In order to manufacture the valve from the preselected polymer material,the characteristics and composition of which have been describedpreviously, a mould 16 (which may be seen in FIG. 2A) provided with ashaft 18 and shaped in such a way that the polymer forms the profile ofvalve 9 when it becomes attached to outer surface 20 of mould 16 isprepared. Mould 16, which in the example illustrated has a shape whichcan be inscribed in a gently tapering cylinder or frustoconical shapehas a lateral surface 20 a which extends along a longitudinal axis A ofthe mould and a front surface 20 b which is projected along axis A inthe plane of confluence of the leaflets or the plane which contains theY-shaped line where the flexible leaflets of valve 9 are joined at thetop. Annular support 10, to which the base of leaflets 12 will adherealong their lower arch, is then made of one piece with mould 16.

FIG. 3 shows the circuit diagram for a portion of a spray machine 22 forthe manufacture of heart valve 9. In a first stage of the process ofvalve manufacture according to the invention the mould and the supportare joined together in one piece, the assembly forming a former 24, andcaused to rotate about longitudinal axis A, for example by attachingshaft 18 of the former to a rotating tailpiece 26 located on machine 22.

A pair of sprays 28 is orientated in such a way as to direct two sprayjets 30 generated by respective nozzles onto former 24 along a directionwhich is substantially transverse with respect to longitudinal axis A.

In all this description and the claims the terms and expressionsindicating positions and orientations, such as “longitudinal”,“transverse”, “vertical”, or “horizontal” relate to longitudinal axis A.

Each spray 28 is fed separately through corresponding tanks 32 in such away as to produce two independent jets 30 which intersect close toformer 24, giving rise to the phenomenon known as phase inversion.Optionally the sprays can be orientated, including independently, insuch a way as to cause jets 30 to converge or diverge, so as toconcentrate or dilute the polymer in the intersection zone.

One spray respectively will be fed with a polymer solution, while theother will generate a flow of non-solvent which by intersecting the jetof polymer solution will give rise to precipitation of the polymer onthe former. Deposition of the polymer on former 24 will give rise to athree-dimensional filamentous structure of the “non-woven” type.

Qualities of the filamentous structure such as porosity, thickness andother morphological characteristics can be adjusted by adjusting thestrength of the jets by means of a central control unit 34, altering theorientation of the jets and/or their position with respect to thelongitudinal axis of former 24. According to one embodiment of theinvention sprays 28 are positioned on a powered carriage 36 which canmove laterally along a direction parallel to longitudinal axis A of theformer in such a way as to vary the point of incidence of the jets alongthe length of longitudinal axis A.

In an embodiment which is not illustrated the sprays may be attached tothe powered carriage by means of spherical connectors which make itpossible to orientate the axis of the jets in such a way that they arealso incident on the former in directions which are not perpendicularwith respect to axis A.

Preferably a suction head 38 is located on one side opposite the nozzleswith respect to longitudinal axis A of the former in such a way as toremove substances which do not precipitate on the former. Head 38 maymove longitudinally in synchrony with the similar movement of thenozzles.

Conveniently, once processing with the jets orientated to generatedeposition of the polymer on the former in a direction substantiallytransverse with respect to longitudinal axis A has been completed, orwhen the polymer deposited on lateral surface 20 a of the mould hasachieved the desired uniformity and thickness, the former is caused torotate 90° towards the sprays so that the jets produced by the nozzlesare incident on front surface 20 b of the mould.

According to an embodiment which is not illustrated it is possible toarrange machine 22 in such a way that instead of causing the former torotate (for example by removing shaft 18 from rotating tailpiece 26 andsecuring it to a supporting plate 40, as may be seen in FIG. 4C), thesprays can be rotated through 90° in such a way as to locate the jetsfrontally with respect to the former, or have the effect that the jetsintersect along a direction parallel to or coincident with longitudinalaxis A. Similar positioning of the sprays may for example be achieved bycausing the carriage to move along a curved guide track which intersectslongitudinal axis A.

According to a further embodiment of the invention (not illustrated),after a preliminary layer of polymer material has been deposited ontoformer 24 (that is interrupting the stage of depositing polymer ontolateral surface 20 a of the former before the said polymer has achievedthe desired final thickness), it is possible to cover this material witha thin reinforcing mesh, in the form of a caul, preferably made usingthreads of elastomer material as an interconnected warp, whose diametermay vary between 10 and 100 microns and the size of the mesh opening ofwhich may vary between 0.2 and 2.0 mm. The elastomer threads may be madeof different resilient materials, for example: urethane polyester(PEsU), urethane polyether (PEtU), urea polyurethane (PUR) or thosebased on urethane polycarbonate (PCU) and urethane polycarbonate(PCU)—polydimethylsiloxane (PDMS) copolymers. Possibly, after depositionof the polymer onto lateral surface 20 a of the former has beeninterrupted (before the said polymer has achieved the desired finalthickness), a similar preliminary layer of material may also bedeposited on front surface 20 b of the former in order to then insertthe reinforcing mesh.

Once inserted the elastomer mesh matches the geometry of the former andbecomes incorporated with the material previously deposited upon it.After this stage deposition of polymer on former 24 is continued untilthe thin mesh is completely incorporated in the thickness of the valveleaflets, and the desired thickness and uniformity of the materialcoating the former is achieved. The presence of the elastomer meshwithin the valve leaflets is intended to increase their mechanicalresistance to fatigue, preventing possible failure and tearing of theleaflets.

Once this cycle of depositing polymer onto the former has beencompleted, any excess solvent is removed, for example by immersion indistilled water heated to approximately 60° C.

The former is then housed in an outer mould 42, which may be seen inFIG. 5B. Preferably outer mould 42 comprises a body 44 on which Y-shapedgrooves 46 are conveniently excavated, flowing towards a central point Pin which the shaft of the former is inserted.

A modular outer mould 48 comprises separate portions or modules 48 awhich can slide within grooves 46 in body 44 in such a way as to closeonto the former, adhering thereto so as to impart the desired curvatureon leaflets 12. In fact said modules 48 a have an internal surface whoseshape imparts the preselected profile of the leaflets onto the non-woventissue deposited on the former. In the case illustrated here, becausethe leaflets of valve 9 are three in number, matrix 48 is subdividedinto the same number of modules 48 a.

Mould modules 48 a are then pressed radially against former 24 so as toimpart the shape of the valve as designed onto the precipitated polymer;the pressure of the outer mould onto the former gives rise to a partialescape of polymer material through the gaps between the modules, due tocompression of the material within the outer mould. This compressiveaction is maintained during the subsequent stages of the process untilthe mould is reopened.

In order to do this, the mould, once the modules have been pressedagainst the former so as to form an assembly of cylindrical shape, isheld in the closed position by means for example of a metal ring 50 insuch a way that subsequent stages of the process do not allow thepressed polymer material to expand and the modules of the mould to moveapart.

The assembly of former, outer mould and metal containing ring is placedin water heated to approximately 60° C. or in a heated stove andsubsequently in water heated to approximately 60° C. for the timerequired for complete cross-linking of the material and removal of thesolvent. The force of the outer mould also favours compaction of thedeposited polymer composite structure/reinforcing mesh of elastomerthread, where the stage of covering the former with the said reinforcingmesh is provided.

Once the heat cycle has been completed and the polymer materials havebecome consolidated the aforesaid assembly is removed from the heatedbath or stove and subsequent heated bath. The excess material leavingmould 48 through the compressive force exerted by the outer mould ontothe former is removed by suitable means (for example a knife 52 asillustrated in FIG. 5E or laser cutting).

Finally modules 48 a of the outer mould are separated and the mouldopened in this way allows the former to be extracted, after which mould16 is separated from the heart valve finally formed by the deposition ofpolymer onto the outer part of annular support 10 (lower ring 10 asurmounted by a wavy crown formed of three rounded projections 10 b).

The advantage accomplished is that of obtaining a heart valve of polymermaterial made in such a way that the polymer material is dosed in anoptimal way, at the same time ensuring maximum flexibility and accuracywhen defining the valve's structural parameters.

Different aspects and embodiments of a technique for the manufacture ofpolymeric heart valves according to the invention have been described.It is intended that each embodiment should be capable of being combinedwith any other embodiment. The invention is also not limited to theembodiments described, but may be varied within the scope defined by theappended claims.

What is claimed is:
 1. A process for manufacturing a heart valve made ofa polymer material, comprising: a) providing a mould shaped so as toreplicate a profile to be conferred upon a valve; b) inserting anannular support onto the mould, so that the mould and support assemblyforms a former; c) providing an apparatus for depositing a polymermaterial onto the former, which comprises a pair of spray guns arrangedtransversely with respect to a longitudinal axis of the former; d)rotating the former about the longitudinal axis; e) feeding one spraygun separately with a polymer solution comprising: (i) a copolymercontaining an intrachain silicone [polydimethylsiloxane (PDMS)] and apolymer selected from the group consisting of a fluorinated poly(carbonate-urethane) (F-PCU), a polycarbonate urethane (PCU), apolyether urethane (PEtU), a polyurethane urea (PUR), a polycaprolactone(PCL); (ii) an extrachain functionalized PDMS, terminating in twodiacetoxy silyl groups, which is able to cross-link itself therebyforming a semi-interpenetrating polymer network(semi-IPN) with thecopolymer (i); and (iii) a solvent; and the other spray gun with anon-solvent for the polymer solution, said non-solvent being selectedfrom the group comprising water, alcohols and mixtures thereof, so as togenerate two jets that intersect along a direction substantiallytransverse to said longitudinal axis; f) keeping the jets focused on oneor more sections of a lateral surface of the former until desiredparameters of polymer thickness and distribution on the lateral surfaceof the former are satisfied; g) directing the jets to impact against afront surface of the former; h) keeping the jets focused frontallyagainst the former, until the desired parameters of polymer thicknessand distribution over the entire front surface of the former aresatisfied; i) eliminating residual solvent traces; j) inserting theformer into an outer mould comprising outer mould modules; k) radiallycompressing the former within the modules, continuing to exercise thecompression force during subsequent process operations; l) heating theouter mould containing the former until cross-linking of the polymermaterial deposited on the former is complete; m) removing excessmaterial from a resulting polymeric valve; n) opening the mould,removing the radial compression force of the outer mould against theformer, and extracting the former from the outer mould; and o) removingthe polymeric valve, including a support ring, from the mould.
 2. Theprocess according to claim 1, wherein the copolymer (i) contains afluorinated poly (carbonate-urethane) (F-PCU) and an intrachain silicone[polydimethylsiloxane(PDMS)], and the copolymer is present in thepolymer solution at a concentration ranging from 1% to 3% w/v per volumeof the solution.
 3. The process according to claim 2, wherein theintrachain silicone (PDMS) is present as about 20% (w/w) of the totalweight of the co-polymer.
 4. The process according to claim 1, whereinthe solvent is selected from the group comprising tetrahydrofuran,dioxane, dimethylacetamide and mixtures thereof.
 5. The processaccording to claim 4, wherein the solvent is a 1:1 mixture (v/v) oftetrahydrofuran and dioxane or tetrahydrofuran and dimethylacetamide. 6.The process according to claim 1, wherein the extrachain functionalizedPDMS terminating in two diacetoxy silyl groups is present in the polymersolution at a concentration varying between 30% and 60% (w/w) of thetotal weight of polymer material.
 7. The process according to claim 1,wherein the non-solvent is selected from the group comprising water,ethyl alcohol, propyl alcohol, benzyl alcohol and mixtures thereof. 8.The process according to claim 7, wherein the non-solvent containspullulan and/or gelatin in solution.
 9. The process according to claim1, wherein during operations (f) and/or (g) and/or (h) the jets are madeto converge or diverge with respect to directions imposed on the jets inprevious operation/operations, to adjust a polymer density in the areain which the aforesaid jets intersect.
 10. The process according toclaim 1, wherein operation (f) is carried out by moving the spray gunslaterally along a direction parallel to the longitudinal axis.
 11. Theprocess according to claim 1, wherein operation (g) is carried out whilekeeping the jets oriented as in operation (f), and rotating the formerso that the longitudinal axis is arranged parallel to said direction ofthe jets.
 12. The process according to claim 1, wherein betweenoperation (f) and operation (g), or between operation (h) and operation(i), there is interposed the operation of coating the former with areinforcing resilient mesh, said operation being followed respectivelyby repeating operation (f) or by repeating operations (f) to (h), untildesired parameters of polymer thickness and distribution on the formerare satisfied.
 13. The process according to claim 1, wherein atoperation (b) a support ring comprises a wavy crown formed by threerounded projections, mutually radiused at a bottom by arched sections,rounded projections having a height of between 13 mm and 3 mm measuredfrom a top of the projection to a lower ring.
 14. A polymeric heartvalve, wherein it is obtainable by a process for manufacturing a heartvalve made of a polymer material, and in that the polymeric heart valvehas a single-piece polymer structure without discontinuities, whereinthe process comprises: a) providing a mould shaped so as to replicate aprofile to be conferred upon a valve; b) inserting an annular supportonto the mould, so that the mould and support assembly forms a former;c) providing an apparatus for depositing a polymer material onto theformer, which comprises a pair of spray guns arranged transversely withrespect to a longitudinal axis of the former; d) rotating the formerabout the longitudinal axis; e) feeding one spray gun separately with apolymer solution comprising: (i) a copolymer containing an intrachainsilicone [polydimethylsiloxane (PDMS)] and a polymer selected from thegroup consisting of a fluorinated poly (carbonate-urethane) (F-PCU), apolycarbonate urethane (PCU), a polyether urethane (PEtU), apolyurethane urea (PUR), a polycaprolactone (PCL); (ii) an extrachainfunctionalized PDMS, terminating in two diacetoxy silyl groups, which isable to cross-link itself thereby forming a semi-interpenetratingpolymer network(semi-IPN) with the copolymer (i); and (iii) a solvent;and the other spray gun with a non-solvent for the polymer solution,said non-solvent being selected from the group comprising water,alcohols and mixtures thereof, so as to generate two jets that intersectalong a direction substantially transverse to said longitudinal axis; f)keeping the jets focused on one or more sections of the lateral surfaceof the former until the desired parameters of polymer thickness anddistribution on a lateral surface of the former are satisfied; g)directing the jets to impact against a front surface of the former; h)keeping the jets focused frontally against the former, until desiredparameters of polymer thickness and distribution over the entire frontsurface of the former are satisfied; i) eliminating residual solventtraces; j) inserting the former into an outer mould comprising outermould modules; k) radially compressing the former within the modules,continuing to exercise the compression force during subsequent processoperations; l) heating the outer mould containing the former untilcross-linking of the polymer material deposited on the former iscomplete; m) removing excess material from a resulting polymeric valve;n) opening the mould, removing the radial compression force of the outermould against the former, and extracting the former from the outermould; and o) removing the polymeric valve, including a support ring,from the mould.